I am proposing to: 1) separate T, B, and Null subpopulation of lymphocytes into isolated subclasses using lectin affinity techniques; 2) define the cytotoxic mechanism by which lymphocytes kill target cells; and 3) functionally characterize the lymphocytes obtained from normal and inflammatory-bowel-disease (IBD) intestine. The isolation of defined human lymphocyte subclasses of subpopulations is necessary in order to identify and subsequently modulate the cells which control the immune response. Understanding the biochemical events which allow cytotoxicity is crucial in order to be able to manipulate the events which allow lymphocytes to kill target cells during an inflammatory reaction. Finally, we will employ our current immunologic capabilities and those which we will develop from examining lymphocyte subclasses and cytotoxic mechanism in order to investigate two areas of gastrointestinal immunology: 1) the functional characteristics of normal intestinal lymphocytes; and 2) the abnormal functional characteristics of lymphocytes from the inflammed intestine of IBD patients. Through these studies, therefore, we plan to attempt to: 1) define the cellular immunopathology associated with IBD; and 2) by expanding our knowledge of lymphocyte subclasses and cytotoxic mechanism, be able to devise approaches to the immunologic manipulation of the IBD process.